A periodic pattern of mRNA secondary structure created by the genetic code

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A periodic pattern of mRNA secondary structure created by the genetic code

Publisher
Oxford University Press
Publication Date
Jan 01, 2006
Source
PMC
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Abstract

A periodic pattern of mRNA secondary structure created by the genetic code Svetlana A. Shabalina*, Aleksey Y. Ogurtsov and Nikolay A. Spiridonov1 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA and 1Division of Therapeutic Proteins, Center for Drug Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA Received March 2, 2006; Revised March 21, 2006; Accepted April 5, 2006 ABSTRACT Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the rela- tionship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleo- tide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both pro- tein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA second- ary structure, which is likely to be important for tran- script stability and translation. We also demonstr

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